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Rabies

 

Rabies is a preventable viral disease of mammals most often transmitted through the bite of a rabid animal. The vast majority of rabies cases reported in Yugoslavia each year occur in foxes. Domestic animals account for less than 10% of the reported rabies cases, with cats most often reported rabid, and occasionally in dogs, cattle, sheep and goats.

Rabies virus infects the central nervous system, causing fatal encephalitis and ultimately death. Early symptoms of rabies in humans are nonspecific, consisting of fever, headache, and general malaise. As the disease progresses, neurological symptoms appear and may include insomnia, anxiety, confusion, slight or partial paralysis, excitation, hallucinations, agitation, hyper salivation, difficulty swallowing, and hydrophobia. Death usually occurs within days of the onset of symptoms.

Public health importance of rabies

Over the last 100 years, rabies in the Yugoslavia has changed dramatically. More than 90% of all animal cases reported annually now occur in wildlife; In northern part of country urban rabies was eliminated before 1960, in Central Serbia at the end of seventies and in Kosovo and Metohija in early 1980. The principal rabies hosts today are foxes. The latest human deaths in the Yugoslavia were registered in 1980. on Kosovo i Metohija. Modern prophylaxis has proven with 100% successful. In Yugoslavia, animals bite about 10.000 persons annually. Only 10% of them are treated against rabies.

Rabies prevention

Post exposure prophylaxis in Yugoslavia is organized over the Net of Antirabic stations in Institutes of Public Health or Clinics for Infective Diseases across the country and it is free of coast for all of the patients. In last 10 years HRIG is produced in Yugoslavia, with high quality and good potency. Since 1990 the Institute for Blood Transfusion in Belgrade and Pasteur Institute in Novi Sad have been producing HRIG. Nowadays human rabies vaccine from cell culture is imported but in few last years we developed human rabies vaccine on BHK cell culture for human use. Now it is in clinical trails on human volunteers. We have good results in all with high antibodies titer and mild adverse reaction at the inoculation site.


The Virus

 

Classification

Rabies virus belongs to the order Mononegavirales, viruses with a nonsegmented, negative-stranded RNA genome. Within this group, viruses with a distinct "bullet" shape are classified in the Rhabdoviridae family, which includes at least three genera of animal viruses, Lyssavirus, Ephemerovirus, and Vesiculovirus. The genus Lyssavirus includes rabies virus, Lagos bat, Mokola virus, Duvenhage virus, European bat virus 1 & 2 and a newly discovered Australian bat virus.

Structure

Rhabdoviruses are approximately 100-300 nm long and 75 nm wide. The rabies genome encodes five proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and polymerase (L). All rhabdoviruses are having two major structural components: a helical ribonucleoprotein core (RNP) and a surrounding envelope. In the RNP, the genome RNA is tightly encased by the nucleoprotein. Two other viral proteins, the phospoprotein and the large protein (or polymerase) are associated with the RNP. The glycoprotein forms approximately 400 trimeric spikes that are tightly arranged on the surface of the virus. The M protein is associated both with the envelope and the RNP and may be the central protein of rhabdovirus assembly. Rabies virions are bullet-shaped with 10-nm spike-like glycoprotein peplomers covering the surface. Rabies has a genome of RNA. The rabies genome contains 5 genes that encode 5 proteins designated as N, P, M, G, and L. The arrangement of these proteins and the RNA genome determine the structure of the rabies virus. The rabies virus genome is single-stranded, antisense, nonsegmented, RNA of approximately 12 kb. There is a leader (LDR) of 50 nucleotides, followed by N, P, M, G, and L genes.

Replication

The fusion of the rabies virus envelope to the host cell membrane (adsorption) initiates the infection process. The interaction of the G protein and specific cell surface receptors may be involved. After adsorption, the virus penetrates the host cell and enters the cytoplasm by pinocytosis. The virions aggregate in the large endosomes (cytoplasmic vesicles). The viral membranes fuse to the endosomal membranes, causing the release of viral RNP into the cytoplasm. Since lyssaviruses have a linear single-stranded, negative-stranded ribonucleic cid (RNA) genome the complementary "positive" strand of RNA must be transcribed before virus replication. A viral polymerasease transcribes the negative strand of RNA into leader RNA and five capped and polyadenylated mRNAs, which are translated into proteins. Translation, which involves the synthesis of the N, P, M, G and L proteins, occurs on free ribosomes in the cytoplasm. Within the central nervous system (CNS), there is preferential viral budding from plasma membranes. Conversely, virus in the salivary glands buds primarily from the cell membrane into the acinar lumen. Specific viral budding into the saliva coupled with virus-induced behavioral changes, maximizes the chance of viral perpetuation through the directed bite and infection of a new host.

Immunity after vaccination

The history of active immunization by vaccine began 115 years ago with Louis Pasteur, who sought a post exposure vaccination against rabies in man. Pasteur protected a 9-year old boy after a rabid dog bite, using dried neural cord as a vaccine. Since Pasteur, vaccination schemes have been based on a continuous vaccine stimulus given for many days and/or multiple injections on the first day. The firs generation type of vaccine (nerve tissue culture) fails to fulfill the present standards of an efficient and safe immunoprophylaxis due to its low protective efficiency, high rate of neurocomplications and death rate. Current immunoprophylaxis is based on inactivated cell culture vaccine. Early, high, and long-lasting antibody induction became the criterion of a successful vaccination regimen.

Development of WHO approved BHK -21 (baby hamster kidney) cell culture vaccine request investigation immune response and its protective effects in man. Pasteur Institute in Novi Sad was beginning vaccination of human volunteers with this vaccine and our first results are very good.


 
 
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